Folate cofactors exist intracellularly as polyglutamate derivatives. The discovery that certain antifolate drugs are converted to similar polyglutamates has raised the possibility of a role for such derivates in chemotherapy. Using dihydrofolate reductases (DHFR) isolated from various animal livers certain comparative aspects of DHFR inhibition by polyglutamyl derivates of the drugs methotrexate (MTX) and 10- deazaaminopterin (10-DAM) as compared with the potent inhibitory properties of the corresponding monoglutamates were investigated. The most striking effects were seen with sheep liver DHFR. Polyglutamylation of MTX causes stepwise increases in inhibition. Six Glu residues is 3-X more inhibitory than the monoglutamate. Increasing the Glu chain on 10-DAM decreases the inhibitory effects up to a chain length of 3. Further increases now result in increasing inhibition. The kinetic parameters of dihydropteroyl-perntaglutamate and dihyropteroylglutamate (dihydrofolate) appear to be identical in this study. However, when the pentafglutamate is used as substrate instead of dihydrofolate, the degree of inhibition is correspondingly decreased 2- to 5- fold for both the MTX and 10-DAM pentaglutamate derivatives. The amount of carotenoids appearing in the plasma of normal men under standardized conditions is highly variable, whereas all subjects ingesting pure beta-carotene gave maximum responses in about 30 hr, the magnitude of the responses varied at least 3-fold. Beta -carotene when fed as the pure compound was comparable to the same dose from cooked carrots. Study of the plasma response to different dietary carotenoid sources revealed that plasma carotenoid concentrations do not accurately reflect dietary intake of certain pro-vitamins, ie., lutein, lycopene, etc.